Molecular mechanisms underlying the neuroendocrine occurrence, biosynthesis, molecular characteristics and function of neuroendocrine peptides and proteins are being studied, with current emphasis on the neuropeptide hormones oxytocin and vasopressin and associated neurophysins (NP's). An hypothesis has been examined that biosynthetic precursors of the neurohypophysial hormones adopt a defined conformational organization upon completion of translation and that this organization helps regulate the production of active peptides produced in neuroendocrine pathways which make the precursors. A method devised to produce biosynthetic precursors and, ultimately, sequence modeled and site specific mutants was used to prepare a semisynthetic oxytocin/neurophysin precursor analog. An evaluation of structural characteristics of the semisynthetic precursor showed that the precursor is a well-ordered, folded molecule which can form self-associated species. The latter are likely to be the prevailing forms in neurosecretory granules in which enzymatic processing occurs. Evaluation of the impact of these characteristics on enzymatic processing is in progress, by comparing rates and products of processing of intact precursors to these properties for synthetic fragments containing processing sites. Separately, evaluation has been made of peripheral sites of occurrence of the hormone/NP neuroendocrine system, including the ovary and peripheral neurons. The relationships of ovarian molecular species to those produced in the hypothalamoneurohypophysial pathway are being studied. The results argue not only that the ovary is a likely site of local synthesis of both oxytocin and neurophysin-related molecules, but also that multiple forms of oxytocin are produced and accumulated in this site. The data help define the relationship between molecular mechanisms which occur in different neuroendocrine sites.